The following studies will be performed to increase understanding of mechanisms of organic anion transport and interactions of compounds in that transport, and thus to facilitate treatment of liver conditions and rational use of therapeutic agents requiring hepatic detoxication and excretion. 1) Develop and test a model of bilirubin metabolism in the whole animal. 2) Determine the relationship of bile acid metabolism to fasting hyperbilirubinemia. 3) Quantitate the effect of bile acids on bile formation (ductular as well as hepatocytic). The hypotheses developed in each of those studies will be tested on the three animal models available to our laboratory: 1. Mutant Shouthdown sheep with an inherited hepatic anion transport defect affecting primarily the process of uptake from plasma to liver; 2. Mutant Corriedale sheep with an inherited hepatic anion transport defect affecting excretion; and 3. the fasted pony which exhibits a reproducible change in hepatic anion uptake.